GOAL: The aims of our study were to investigate autonomic modifications in wakefulness and sleep in a cohort of patients with acute ischemic stroke and to evaluate whereas these modifications were dependent by sleep stage and stroke lateralization. MATERIALS AND METHODS: We prospectively enrolled 42 patients (22 men and 20 women, mean age: 69.8 +/- 11.3; range: 32-92 years) with acute ischemic stroke. All participants underwent a full-night polysomnography. As index of autonomic nervous system we used Heart Rate Variability (HRV), analyzed in wakefulness and during different sleep stages. First, we compared our cohort with a control group of 42 healthy subjects, matched for age and sex. Subsequently, we divided our cohort in 2 subgroups according stroke lateralization (21 right, 21 left) and compared with control population. FINDINGS: We observed significant modifications of HRV parameters mainly for the right lesions. In particular, we observed a prevalent parasympathetic tone during the wake (low frequency/high frequency [LF/HF]: right: 2.99 +/- 8.91; controls: 3.88 +/- 3.42; P < .01) and during REM (LF/HF right: 0.03 +/- 1.58; controls: 2.92 +/- 3.97; P < .01) accompanied by a significant reduction of sympathetic tone during REM (LF right: 23.85 +/- 44.42 n.u.; controls: 51.13 +/- 32.25 n.u.; P < .01), and by a reduction of parasympathetic tone during N3 (HF right: 28.09 +/- 37.67 n.u.; controls: 43.08 +/- 68.39 n.u.; P < .01). CONCLUSIONS: Our study indicates that autonomic dysfunctions in acute ischemic stroke are prevalent in right-side lesions and strictly dependent by sleep-wake stage.